In a recently completed study we observed that chemically-induced lung tumors in athymic nude mice had some unusual histological features when compared with tumors in normal mice of the same age. These features included prominence of small, basophilic, atypical cells, and invasion into the parenchyma of the lung and through the pleural surface. These results suggested that mouse lung tumors may progress toward malignancy more rapidly than normal in the absence of thymus-dependent immune system function. As a test of this hypothesis we propose to maintain carcinogen-treated nude mice under pathogen-free conditions, to permit long-term survival of the mice and full opportunity for manifestation of any malignant tendencies. A corollary of our hypothesis is that the lung tumors in the nudes may be more antigenic than normal. We will test this idea with in vivo and in vitro assays of cell-mediated immunity developed in mice challenged with nude or normal tumor cells. Another carcinogenesis experiment with the nudes will involve chronic, oral administration of a low dose of an environmental nitrosamine carcinogen, dimethylnitrosamine. Data published thus far from several laboratories has indicated that nudes do not differ from normal mice with regard to tummor incidence after carcinogen treatment. However, only a few carcinogens and a few routes of administration have been tried, and no lifetime studies have been reported. It is therefore of interest to continue investigations on the subject of susceptibility of nude mice to carcinogens, with special focus on exposure conditions mimicking possible human situations.